Studies on the role of free radicals in cellular injury caused by mineral particles and metal ions were concluded. They showed that hydroxyl radicals, generated by metal-mediated Fenton-like reactions, play an important role in the mechanism of silica-induced activation of the nuclear transcription factor NFkB. The previously reported inhibition by tumor necrosis factor-alpha (TNF) of quartz-induced neoplastic transformation of BALB/3T3 cells was re-evaluated on the basis of the induction by TNF of manganese-dependent superoxide dismutase (Mn-SOD). The dependence of quartz-induced transformation on an oxygen radical mechanism was demonstrated by its strong inhibition by the free radical scavenger, dimethylsulfoxide. That properties of the surface chemistry of crystalline silica directly determine its biological activity was shown by tests on a sample of cristobalite, which was highly toxic on rat lung alveolar epithelial AE6 cells, but lost most of its activity after heating at 800 degrees C and was completely nontoxic after heating at 1300 degrees C: the heat treatment removed the reactive surface hydroxyl and ionized groups replacing them with unreactive oxygen bridges (siloxanes).